Transcutaneous immunization (TCI) is a novel immunization strategy in which vaccine antigens are placed on the intact skin. We have demonstrated that application of cholera toxin (CT) or the related protein heat labile enterotoxin (LT), to the skin surface results in potent serum anti-toxin responses. In the case of CT, we have explored the mucosal immunity induced by TCI and identified anti-toxin IgG and IgA in the sera, lung extracts, and stools of immunized animals. In contrast to oral and parenteral routes of administration, introduction of CT and LT by TCI is not associated with toxicity-a sequelae which has hindered development of vaccines against cholera and traveler's diarrhea. We hypothesize that generation of high-titer antibodies against these toxins through TCI will greatly improve the efficacy of vaccines against cholera and traveler's diarrhea. The purpose of this proposal is to evaluate the effectiveness of TCI in generating toxin antibody responses that will protect against oral toxin challenge. We envision that TCI with CT or LT would be used in conjunction with, or as a replacement for, the current whole cell cholera vaccine. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE